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Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: A systematic review and meta-analysis with evidence from up to 331 175 individuals.
Hum. Mol. Genet. 24, 3582-3594 (2015)
Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (β = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (β = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
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Publication type
Article: Journal article
Document type
Review
Keywords
Genome-wide Association; Early-onset Obesity; Cardiovascular-disease; Genetic Association; Chinese Population; Identifies Common; Health-assessment; Extreme Obesity; Adult Obesity; Confer Risk
Language
english
Publication Year
2015
HGF-reported in Year
2015
ISSN (print) / ISBN
0964-6906
e-ISSN
1460-2083
Journal
Human Molecular Genetics
Quellenangaben
Volume: 24,
Issue: 12,
Pages: 3582-3594
Publisher
Oxford University Press
Publishing Place
Oxford
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Genetic Epidemiology (IGE)
Institute of Diabetes Research and Metabolic Diseases (IDM)
POF-Topic(s)
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504091-004
G-504091-002
G-504100-001
G-504000-002
G-504000-007
G-504091-002
G-504100-001
G-504000-002
G-504000-007
WOS ID
WOS:000355674400024
PubMed ID
25784503
Erfassungsdatum
2015-04-15